Electromagnetic field-enhanced chiral dimanganese trioxide nanoparticles mitigate Parkinson’s disease

The misfolding and aggregation of α-synuclein (α-syn) is closely associated with Parkinson’s disease (PD). Here, chiral dimanganese trioxide (Mn2O3) nanoparticles (NPs) were prepared for PD treatment enhanced by a noninvasive electromagnetic field (MF). The affinity constants of D-NPs toward α-syn monomer (mono) or α-syn fibril were 3.5 times or 5.2 times higher, respectively, than those of L-NPs, and the mechanical force generated by NPs under a MF further promoted the interaction between NPs and α-syn to amplify the difference between L-NPs and D-NPs. As the synergy effect of the preferentially affinity ability and MF-induced mechanical forces, D-NPs exhibited a better inhibitory efficiency on α-syn fibrillization than L-NPs. Furthermore, after differentially cellular uptake of L-/D-NPs via the caveolin-mediated pathway, as reactive oxygen species (ROS)-scavengers, D-NPs possess higher efficiency in decreasing intracellular ROS level than L-NPs to provide higher cytoprotective efficiency to neuron cells. In vivo data showed that after treatment with D-NPs under a MF for 60 days, α-syn concentration in the cerebrospinal fluid of PD mice decreased 81%, while dopamine level in the brain of PD mice increased 2.3-fold. These findings indicated the potential of utilizing the synergic interplay of chiral NPs and MF for treating disease and opened a new path to explore the nanoscale chirality for regulating the biological effect.